Characterizing the effects of triclosan and triclocarban on the intestinal epithelial homeostasis using small intestinal organoids.

Intestinal epithelium has the largest surface of human body, contributes dramatically to defense of toxicant-associated intestinal injury. Triclosan (TCS) and triclocarban (TCC), extensively employed as antibacterial agents in personal care products (PCPs) and healthcare facilities, caused serious damage to human intestine. However, the role of the intestinal epithelium in TCS/TCC-induced intestinal toxicity and its underlying toxic mechanisms remain incompletely understood. In this study, a novel 3D intestinal organoid model was utilized to investigate that exposure to TCS/TCC led to a compromised self-renewal and differentiation of intestinal stem cells (ISCs). Consequently, this disrupted intestinal epithelial homeostasis ultimately caused a reduction in nutrient absorption and deficient of epithelial defense to exogenous and endogenous pathogens stimulation. The inhibition of the Wnt signaling pathway in intestinal stem cell was contributed to the intestinal toxicity of TCS/TCC. These results were further confirmed in vivo with mice exposed to TCS/TCC. The findings of this study provide evidence that TCS/TCC possess the capacity to disturb the homeostasis of the intestinal epithelium, and emphasize the credibility of organoids as a valuable model for toxicological studies, as they could faithfully recapitulate in vivo phenomena.

Evaluating the Effects of Perinatal Exposures to BPSIP on Hepatic Cholesterol Metabolism in Female and Male Offspring ICR Mice.

BACKGROUND: A broad suite of bisphenol S (BPS) derivatives as alternatives for BPS have been identified in various human biological samples, including 4-hydroxyphenyl 4-isopropoxyphenylsulfone (BPSIP) detected in human umbilical cord plasma and breast milk. However, very little is known about the health outcomes of prenatal BPS derivative exposure to offspring. OBJECTIVES: Our study aimed to investigate the response of hepatic cholesterol metabolism by sex in offspring of dams exposed to BPSIP. METHODS: Pregnant ICR mice were exposed to 5µg/kg body weight (BW)/day of BPSIP, BPS, or E2 through drinking water from gestational day one until the pups were weaned. The concentration of BPSIP, BPS, or E2 in the plasma and liver of pups was determined by liquid chromatography-tandem mass spectrometry. Metabolic phenotypes were recorded, and histopathology was examined for liver impairment. Transcriptome analysis was employed to characterize the distribution and expression patterns of differentially expressed genes across sexes. The metabolic regulation was validated by quantitative real-time PCR, immunohistochemistry, and immunoblotting. The role of estrogen receptors (ERs) in mediating sex-dependent effects was investigated using animal models and liver organoids. RESULTS: Pups of dams exposed to BPSIP showed a higher serum cholesterol level, and liver cholesterol levels were higher in females and lower in males than in the controls. BPSIP concentration in the male liver was 1.22±0.25 ng/g and 0.69±0.27 ng/g in the female liver. Histopathology analysis showed steatosis and lipid deposition in both male and female offspring. Transcriptome and gene expression analyses identified sex-specific differences in cholesterol biosynthesis, absorption, disposal, and efflux between pups of dams exposed to BPSIP and those in controls. In vivo, chromatin immunoprecipitation analysis revealed that the binding of ERα protein to key genes such as Hmgcr, Pcsk9, and Abcg5 was attenuated in BPSIP-exposed females compared to controls, while it was enhanced in males. In vitro, the liver organoid experiments demonstrated that restoration of differential expression induced by BPSIP in key genes, such as Hmgcr, Ldlr, and Cyp7a1, to levels comparable to the controls was only achieved when treated with a combination of ERα agonist and ERß agonist. DISCUSSION: Findings from this study suggest that perinatal exposure to BPSIP disrupted cholesterol metabolism in a sex-specific manner in a mouse model, in which ERα played a crucial role both in vivo and in vitro. Therefore, it is crucial to systematically evaluate BPS derivatives to protect maternal health during pregnancy and prevent the transmission of metabolic disorders across generations. https://doi.org/10.1289/EHP14643.

Superior Piezo-/Ferro-Electricity in Antiferroelectric AgxNbO3-δ Thin Films by Nanopillar Local Structure Design.

Antiferroelectrics are fundamental mother compounds critical in developing innovative lead-free piezoelectrics and ferroelectrics and hold great promise for wide-ranging applications in energy conversion and electronic devices. However, harnessing their superior properties presents a significant challenge due to the delicate balance required between their various states. In this study, through the unique design of nanopillar structures to alleviate the local polar heterogeneity, we have achieved significantly improved piezo-/ferro-electricity in classic lead-free antiferroelectric AgxNbO3-δ (x = 1, 0.9, and 0.8) epitaxial thin films. The effective piezoelectric coefficient reaches 440 pm V-1, 1 order of magnitude larger than the stoichiometric AgNbO3, rivaling classic lead zirconate titanate piezoelectrics. Atomic-scale electron microscopy investigations unravel the underlying mechanisms. The nanopillars, characterized by antisite occupancy of both Ag and Nb atoms and forming out-of-phase boundaries with the matrix, reduce the local crystal symmetry via interphase strain. This leads to the creation of flexible multinanodomain structures that significantly facilitate polarization rotation, thus substantially enhancing the piezoelectric performance. This study demonstrates the feasibility of engineering local heterogeneity through nanopillar design, offering a generally applicable method for property improvement of a wide range of antiferroelectrics.

LncRNA SLNCR1 facilitates angiogenesis and tumor growth in melanoma via DNMT1-mediated epigenetically silencing SPRY2.

BACKGROUND: The malignancy of melanoma is attributed to its pronounced invasiveness, extensive vascularization, and rapid tumor cell growth and metastasis. LncRNA SLNCR1 is closely associated with a variety of aggressive tumors. However, our understanding of SLNCR1 influences on malignant melanoma growth metastasis mechanism especially proangiogenic mechanism remains unclear. METHODS: The expression of SLNCR1 was evaluated in melanoma tissues, adjacent tissues, melanoma cell lines. The abilities of SLNCR1 on proliferation, migration, and angiogenesis of HUVECs were detected by CCK-8, flow cytometry, and Western blot assays. The association between SLNCR1, DNMT1, and SPRY2 was assessed by ChIP, RIP, and Western blot assays. The effect of SLNCR1 on tumor growth was determined using a xenograft model in nude mice. RESULTS: SLNCR1 was confirmed to be highly expressed in melanoma tissues and cells. CM from melanoma cells transfected with sh-SLNCR1 attenuated proliferation, migration, and angiogenesis of HUVECs. Moreover, loss of SLNCR1 hindered tumor growth and metastasis, as evidenced by reduced tumor size and weight, as well as angiogenesis. Mechanistic studies revealed that SLNCR1 silenced SPRY2 expression, likely through enhancing DNMT1-mediated DNA methylation of SPRY2 promoter. CONCLUSION: SLNCR1 is an oncogene that interacts with DNMT1 to mediate SPRY2 methylation, thereby suppressing SPRY2 expression and promoting the angiogenesis and tumor growth in melanoma. SLNCR1 may serve as a potential target for melanoma treatment.

Single Crystalline GeSe Van Der Waals Ribbons With Uniform Layer Stacking, High Carrier Mobility, and Adjustable Edge Morphology.

Performance of the group IV monochalcogenide GeSe in solar cells, electronic, and optoelectronic devices is expected to improve when high-quality single crystalline material is used rather than polycrystalline films. Crystalline flakes represent an attractive alternative to bulk single crystals as their synthesis may be developed to be scalable, faster, and with higher overall yield. However, large - and especially large and thin - single crystal flakes are notoriously hard to synthesize. Here it is demonstrated that vapor-liquid-solid growth combined with direct lateral vapor-solid incorporation produces high-quality single crystalline GeSe ribbons with tens of micrometers size and controllable thickness. Electron microscopy shows that the ribbons exhibit perfect equilibrium (AB) van der Waals stacking order without extended defects across the entire thickness, in contrast to the conventional case of substrate-supported flakes where material is added via layer-by-layer nucleation and growth on the basal plane. Electrical measurements show anisotropic transport and a high Hall mobility of 85 cm2 V-1 s-1, on par with the best single crystals to date. Growth from mixed GeSe and SnSe vapors, finally, yields ribbons with unchanged structure and composition but with jagged edges, promising for applications that rely on ample chemically active edge sites, such as catalysis or photocatalysis.

ADSCs encapsulated in Gelatin methacrylate substrate promotes the repair of peripheral nerve injury by SIRT6/PGC-1α pathway.

Peripheral nerve injury is a prevalent disease but the spontaneous recovery of nerve function is protracted and incomplete. Given the damaging of stem cells and fragile of intra-neural structures in the course of stem cell transplantation, our study tried to investigate whether encapsulating adipose derived mesenchymal stem cells (ADSCs) with GelMA could achieve better repair in peripheral nerve injury. PC-12 cells were cultured on the surface of GelMA encapsulating ADSCs and 3D co-culture system was constructed. CCK-8, Real-Time PCR, ELISA, Immunofluorescent Assay and Western Blot were used to evaluate the functionality of this system. Ultimately, nerve conduit containing the 3D co-culture system was linked between the two ends of an injured nerve. ADSCs encapsulated in 5% GeIMA had a better activity than 10% GeIMA. Furthermore, the viability of PC-12 cells was also better in this 3D co-culture system than in co-culture system with ADSCs without GeIMA. The expression of SIRT6 and PGC-1α in PC-12 cells were prominently promoted, and the entry to nuclear of PGC-1α was more obvious in this 3D co-culture system. After silencing of SIRT6, the protein expression level of PGC-1α was inhibited, and the activity of PC-12 cells was significantly reduced, suggesting that ADSCs encapsulated in GelMA upregulated the expression of SIRT6 to induce the level of PGC-1α protein, thereby achieving an impact on the activity of PC-12 cells. In vivo, nerve conduit containing the 3D co-culture system significantly promoted the repair of damaged peripheral nerves. In conclusion, our study demonstrated that 5% GelMA enhanced ADSCs activity, thereby promoting the activity of nerve cells and repair of damaged peripheral nerves by SIRT6/PGC-1α pathway.

Hypocrellin A against intrahepatic Cholangiocarcinoma via multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive and highly lethal cancer with an increasing incidence worldwide that lacks effective treatment regimens. Hypocrellin A (HA), a natural small compound isolated from S. bambusicola, has multiple biomedical activities, including antitumor activity. PURPOSE: We intended to investigate the therapeutic effects of HA on ICC and its potential mechanisms. METHODS: RBE and HuccT1 cell lines were utilized for in vitro experiments. CCK8 assay, colony formation analysis, RTCA, and immunofluorescence staining of ki67 were employed to evaluate the suppression effects of HA on proliferation. The inhibitory effects of HA on cell migration and invasion were evaluate through transwell and wound healing assays, and Hoechst 33,258 staining was performed to evaluate apoptosis. Additionally, we performed transcriptome sequencing and molecular docking for targeting identification, and immunoblotting and immunofluorescence of key molecules for validation. Two in vivo models, HuccT1 xenografts, and the primary ICC model (KRAS/P19/SB) established via hydrodynamic tail-vein injection were implemented. Multiplex immunohistochemistry (mIHC) was used to illustrate the multi-target inhibitory effects of HA. RESULTS: The IC50 values of HA against RBE and HuccT1 cells were 4.612 µM and 10.01 µM for 24 h, as determined through the CCK8 assay. Our results confirmed that HA significantly repressed the proliferation, migration, invasion, and promoted the apoptosis of ICC cells at low concentrations. Moreover, HA exerted its anti-cancer effects through multi-target inhibition of the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. This inhibitory effect was rescued by Recilisib, an activator of the PI3K-AKT-mTOR pathway. Bioinformatics analysis of a multi-center RNA-Seq cohort (n = 90) demonstrated significant associations between these target pathways and the occurrence and poor prognosis of ICC. Animal studies suggested that HA strongly inhibited tumor growth in xenograft ICC models, and repressed the tumor number and size in the liver of primary ICC models by suppressing these three crucial pathways. CONCLUSION: HA, a novel natural small molecule, demonstrated promising therapeutic efficacy against ICC through its multi-target inhibitory effects on the PI3K-AKT-mTOR, MAPK, and STAT3 signaling pathways. Moreover, it exhibited notable therapeutic benefits in a primary ICC model (KRAS/P19/SB), positioning it as a novel therapeutic agent for ICC.

Development and validation of the 5-Dimension Comprehensive Assessment Scale (5DCAS) for assessing physical function and health in axial spondyloarthritis.

OBJECTIVE: To describe the development and validation of a novel patient reported scale, which is a comprehensive assessment of the physical function and health specific for patients with axial spondyloarthritis (axSpA). METHODS: This is a multiphase, mixed methods study. Based on opinion collection and discussions of multidisciplinary consensus meetings and patients, an initial item pool covering all of the ranges of functioning was generated. The item optimization, model fit, response category functioning, differential item functioning, reliability, structure validity, and unidimensionality were tested by confirmatory factor analysis and Rasch measurement theory framework. RESULTS: After the consensus meeting and the two rounds of surveys in patients with axSpA, the initial pool of 135 items was reduced to 25 items formed in five dimensions, which exhibited preferable item reliability, item fit, and person fit to the Rasch model. The Five-Dimensional Comprehensive Assessment Scale (5DCAS) had the best reliability and validity (Kaiser-Meyer-Olkin was 0.919, and the standardized Cronbach's α coefficient was 0.932). The final version of 5DCAS had good unidimensionality, and the Person Separation Index ranged from 0.77 to 0.85. 5DCAS significantly correlated with ASAS-HI, SF-36, BASFI, and disease activity with p values of < 0.001. CONCLUSION: 5DCAS is a novel patient-reported outcome specific to axSpA, and it forms five dimensions providing a linear sum score of 25 items. 5DCAS comprehensively and significantly represents the physical function and health status of patients with axSpA, although its performance needs further validation in future clinical practices. Key Points • The primary goal in the management of axial spondyloarthritis is to maximize health-related quality of life. Except for the current instruments of ASAS-HI, BASFI, or SF-36, the heterogeneous clinical symptoms and rapid updated treat-to-target concept require a new instrument which can comprehensive and significant evaluate the changes of physical function and health-related quality of life due to disease. • 5DCAS is a novel patient-reported outcome specific to axSpA, and it forms five dimensions providing a linear sum score of 25 items, which contained aspect of pain involvement, spine mobility, global body performance and activity, social participation and environment, and mental health. All of the items were set to a 4-point semantic rating scale measuring severity, frequency, or interference from score 0 to 3. Total 5DCAS score ranges from 0 to 75; higher scores represented greater symptom burden and worse physical function. • 5DCAS is a comprehensive, multidisciplinary, and convenient disease outcome measurement specific for axSpA. It provides a new evaluation instrument in clinical trial and treat-to-target clinical remission for patients and physicians, and also provides a sensitive and accurate assessment standard for optimized health benefits.

Detection of Short-Chain Chlorinated Aliphatic Hydrocarbons through an Engineered Biosensor with Tailored Ligand Specificity.

Short-chain chlorinated aliphatic hydrocarbons (SCAHs), commonly used as industrial reagents and solvents, pose a significant threat to ecosystems and human health as they infiltrate aquatic environments due to extensive usage and accidental spills. Whole-cell biosensors have emerged as cost-effective, rapid, and real-time analytical tools for environmental monitoring and remediation. While the broad ligand specificity of transcriptional factors (TFs) often prohibits the application of such biosensors. Herein, we exploited a semirational transition ligand approach in conjunction with a positive/negative fluorescence-activated cell sorting (FACS) strategy to develop a biosensor based on the TF AlkS, which is highly specific for SCAHs. Furthermore, through promoter-directed evolution, the performance of the biosensor was further enhanced. Mutation in the -10 region of constitutive promoter PalkS resulted in reduced AlkS leakage expression, while mutation in the -10 region of inducible promoter PalkB increased its accessibility to the AlkS-SCAHs complex. This led to an 89% reduction in background fluorescence leakage of the optimized biosensor, M2-463, further enhancing its response to SCAHs. The optimized biosensor was highly sensitive and exhibited a broader dynamic response range with a 150-fold increase in fluorescence output after 1 h of induction. The detection limit (LOD) reached 0.03 ppm, and the average recovery rate of SCAHs in actual water samples ranged from 95.87 to 101.20%. The accuracy and precision of the proposed biosensor were validated using gas chromatography-mass spectrometry (GC-MS), demonstrating the promising application for SCAH detection in an actual environment sample.

Potential candidate maternal serum miRNAs for the diagnosis of fetal congenital heart disease.

Congenital heart disease (CHD) is one of the most significant birth defects leading to infant mortality worldwide. Circulating microRNAs (miRNAs) are emerging as novel biomarkers for the detection of cardiovascular diseases. In this study, we aimed to investigate the role of maternal serum miRNAs expression as biomarkers in the diagnosis and prediction of children with CHD. High-throughput sequencing of peripheral blood from pregnant women with abnormal and normal fetal hearts identified 1939 differentially expressed miRNAs, the first 11 of which were selected as predictive biomarkers of CHD. The expression of miRNAs in more clinical samples was then quantitatively verified by reverse transcriptase polymerase chain reaction and the correlation between abnormal miRNAs and CHD was analyzed. Two miRNAs (hsa-miR-3195 and hsa-miR-122-5p) were found to be significantly down-regulated in pregnant women with fetal CHD. By further bioinformatics analysis, we predicted that hsa-miR-3195 and hsa-miR-122-5p could induce CHD by influencing biometabolic processes. hsa-miR-3195 and hsa-miR-122-5p may serve as novel non-invasive biomarkers for prenatal detection of fetal CHD.

An improvement on the assessment of ecosystem services value of urban wetlands under consideration of water yield at regional scale.

Urban wetlands are gaining more attention and showing more important play in the sustainability. Surge findings are attached on the assessment of Wetland Ecosystem Service Value (WESV) in urban areas. While determining WESV in urban areas, it is still difficult to capture the nature of wetlands due to neglecting the impact of related impervious surfaces. It is necessary to improve the existing evaluating methods of WESV when seeking the truth. In order to narrow this issue, based on InVEST model, this study employed Equivalent Factors (EF) to determine WESV in urban areas with a case of Hengyang City, China. The main materials of this study included high-resolution images, DEM, precipitation, evapotranspiration, soil, vegetation, and statistical yearbook of the case. By comparing the uncorrected results with precipitation corrected and water yield corrected results of WESV, this study confirmed that: (1) the corrected results can reflect more real status than uncorrected; (2) in terms of EF, the water yield factor is more conducive to finding the truth than precipitation. Through this study, the water yield factor can effectively reduce the adverse effects of climate and improve the accuracy when determining WESV in urban areas.

Clinical efficacy of refined nursing strategies on early rehabilitation training for postoperative patients with cervical spondylosis.

To investigate the effects of refined nursing strategies on postoperative quality of life, pain level, psychological condition, and other rehabilitation training of patients with cervical spondylosis. This study is a retrospective study, and 500 patients with cervical spondylosis admitted to our hospital from April 2022 to June 2023 were selected as the study objects. They were divided into a control group (250 cases) and an experimental group (250 cases) according to whether they received personalized intensive care. The control group received standard nursing care, while the experimental group was given personalized, high-quality nursing care. The refined nursing strategy comprises individualized rehabilitation training plans, psychological support, nutritional counseling, and pain management. Indicators such as pain level, cervical spine function, quality of life, complication statistics, and nursing satisfaction were employed to evaluate the clinical efficacy of 2 nursing methods. In the pain assessment, patients in the experimental and control groups had pain scores of (1.98 ±â€…0.84) and (5.78 ±â€…0.63), respectively, after the nursing intervention. The reduction in pain for patients in the experimental group was highly significant (P < .05) compared to pre-nursing care. Six months after the commencement of healthcare, the cervical spine function scores of the experimental and control groups were (93.36 ±â€…4.74) and (82.68 ±â€…5.42), respectively. Moreover, the cervical spine function recovery of the experimental group was deemed significant. The experimental group exhibited a lower probability of complications compared to the control group. Additionally, the quality of life was significantly higher in the experimental group than in the control group (P < .05). Improvement time and healing time were significantly shorter in the patients of the experimental group in comparison to the control group. In terms of nursing satisfaction, the experimental group had a significantly higher satisfaction rate of 87.57% than the control group (P < .05). The refined nursing strategy significantly improved the speed and quality of patients' functional recovery. Additionally, the implementation of personalized and comprehensive nursing techniques during postoperative treatment for cervical spondylosis resulted in a significant improvement in patient's quality of life and satisfaction with the treatment process.

Record of microplastic deposition revealed by ornithogenic soil and sediment profiles from Ross Island, Antarctica.

Microplastics (MPs) are a global concern as an emerging pollutant, and the investigation on MPs in Antarctic aids in informing their global pollution assessments. Therefore, there are urgent scientific concerns regarding the environmental behavior, origins, influencing factors, and potential hazards of MPs in Antarctica. This study presents the characteristics of MPs from one ornithogenic sediment profile (coded CC) and two ornithogenic soil profiles (coded MR1 and MR2) from ice-free areas on Ross Island, Antarctica. We explored the potential sources of MPs and the main influencing factors for deposition based on their distribution with depth in the profiles. Through laser-infrared imaging spectroscopy (LDIR), a total of 30 polymer types were identified in all samples, with polyethylene terephthalate (PET) and polyvinyl chloride (PVC) as the dominant types, accounting for more than 70% of the total. The abundance of MPs in the CC sediment profile ranged from 2.83 to 394.18 items/g, while in MR1 and MR2 soil profiles, the abundance ranged from 2.25 to 1690.11 and 8.24 to 168.27 items/g, respectively. The size of MPs was mainly concentrated in the range of 20-50 µm, and possible downward movement of certain polymer types was revealed. From the perspective of temporal variation, we suggest that MPs were heavily influenced by local human activities including scientific research, fishing, and tourism, balanced by protective regulations, while no solid evidence was obtained to support strong influence from biological transport through penguins. This research enhances our understanding on the environmental behavior of MPs in the terrestrial systems of remote polar regions.

Enhanced Transconjunctival Lower Blepharoplasty: A Novel Method for Intraorbital Fat Transposition and Stabilization.

BACKGROUND: The evolution of lower blepharoplasty has shifted from simply removing of orbital septum fat to smoothing of the lid-cheek junction through fat repositioning. This paper adopts a novel technique to transpose and stabilize intraorbital fat during transconjunctival lower blepharoplasty. The tear trough and nasal alar base were filled to correct the pouch while ensuring the blood supply of the fat flap. METHODS: Between September 2019 and June 2022, 104 patients aged between 22 and 49 who underwent bilateral fat flap transposition-nasal alar base filling lower blepharoplasty were selected. The surgical results were assessed by non-operative plastic surgeons according to the Hirmand grading system. Moreover, a self-satisfaction survey was conducted and patients were followed up for at least 6 months to evaluate any complications and surgical outcomes. A high-frequency ultrasound imaging system was used to assess the degree of filling of the tear trough and nasal alar base. RESULTS: All 104 patients were followed up for at least 6 months. The postoperative Hirmand grade was 0 for 96 out of 104 (92.3%) patients. In terms of self-satisfaction assessment, there were 92 out of 104 (88.5%) patients reported satisfaction. Dermatologic ultrasound showed no obvious gaps 6 months after surgery. CONCLUSION: Transconjunctival fat flap transposition combined with nasal alar base filling during lower blepharoplasty has been shown to have a positive postoperative effect and high patient satisfaction. This procedure can preserve the blood supply of the fat flap, reduce the rates of fat absorption and denaturation, and improve facial contour, resulting in a satisfactory repairing effect. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis.

Palatine tonsils are the only air-contacted lymphoid organs that constantly engage in crosstalk with commensal microorganisms and serve as the first handling sites against microbial antigens. While tonsil inflammations have been implicated in various autoimmune diseases, including rheumatoid arthritis (RA), the precise role of tonsillar microbiota in autoimmune pathogenesis remains inadequately characterized. In this study, we profiled the tonsillar microbiota and identified a notable dysbiosis in patients with RA, particularly within the Streptococcus genus. Specifically, patients with RA exhibited an enrichment of pathogenic Streptococcus species, including S. pyogenes, S. dysgalactiae, and S. agalactiae. Colonization with these bacteria significantly exacerbated arthritis severity and increased autoimmune responses in collagen-induced arthritis (CIA). Furthermore, immunization with peptides derived from these pathogenic Streptococcus species directly induced experimental arthritis. Conversely, patients with RA demonstrated a marked deficiency in commensal Streptococcus members, notably S. salivarius. Treatment of CIA mice with S. salivarius attenuated the progression of arthritis and downregulated autoimmune responses. These findings highlight a pathogenic link of tonsillar microbiota with RA, shedding light on their contribution to autoimmunity.

Comparative long-term prognosis of early surgery and surgery after surveillance for patients with ground-glass nodule adenocarcinomas.

To compare the pathological results and long-term survival results of early surgery and surgery after at least one year follow-up for ground-glass component predominant lung adenocarcinoma patients. From January 1, 2013 to August 31, 2017, a total of 279 patients with ground-glass nodules (GGNs) undergoing surgical resection and pathologically proved to be pulmonary adenocarcinoma were included in this study. All patients were divided into early surgery group (ES Group) (210 cases) and surgery after follow-up group (FS Group) (69 cases). Patients in FS group experienced at least one year surveillance. Clinical and imaging features were analyzed by using univariate analysis. After analysis, there was no statistical difference in pathological results and long-term prognosis between the two groups. In the follow-up group, grown GGNs have proved to have more aggressive pathological results. The one-year follow-up may be a feasible management method for patients with ground-glass component predominant GGN.

Systematic profiling of mitochondria-related transcriptome in tumorigenesis, prognosis, and tumor immune microenvironment of intrahepatic cholangiocarcinoma: a multi-center cohort study.

Background: Mitochondrial dysfunction has been shown to play a critical role in cancer biology. However, its involvement in intrahepatic cholangiocarcinoma (iCCA) remains significantly understudied. Methods: RNA sequencing data of 30 pairs of iCCA and paracancerous tissues were collected from the First Affiliated Hospital of Wenzhou Medical University (WMU). The WMU cohort (n = 30) was integrated with public TCGA (n = 30) and GSE107943 (n = 30) datasets to establish a multi-center iCCA cohort. We merged the TCGA and GSE107943 cohorts into an exploration cohort to develop a mitochondria signature for prognosis assessment, and utilized the WMU cohort for external validation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Hallmarker analyses were used for functional interpretation of iCCA associated mitochondria-related genes (MRGs). In addition, unsupervised clustering was performed to identify mitochondria-based iCCA subtypes with the data of three institutions. Further investigations were conducted to examine the impact of mitochondrial dysfunction on drug responses, alteration of the tumor immune microenvironment, and immune responses. Results: Two hundred and sixty-three iCCA-related MRGs were identified to be related to fatty acid metabolism, oxidative phosphorylation, and apoptosis. Through univariate and multivariate Cox, and LASSO analyses, a mitochondria signature with five optimal MRGs was established to evaluate the prognosis of iCCA patients with the AUC values ranged from 0.785 to 0.928 in the exploration cohort. The signature also exhibited satisfactory performance in the WMU cohort with AUC values of 0.817-0.871, and was identified as an independent risk predictor in both cohorts. Additionally, we found that patients with higher mitochondria score with poor prognosis presented lower infiltration levels of CD4+ T-cell, NK cells, and monocytes, and demonstrated higher sensitivity to targeted therapies, including sorafenib. Furthermore, two distant mitochondria-based subtypes were determined, and subtype 2 was associated with shorter survival time and immunosuppressive tumor microenvironment. Finally, the differential protein expression of five key MRGs was verified by Immunohistochemistry. Conclusion: We found mitochondrial dysfunction modulates aberrant metabolism, oxidative stress, immune responses, apoptosis, and drug sensitivity in iCCA. A mitochondria signature and two mitochondria-based iCCA subtypes were identified for clinical risk stratification and immunophenotyping.

Early postoperative core symptoms and their relationship with resilience in oesophageal cancer patients-A multicentre cross-sectional study.

AIM: To assess early postoperative core symptoms in oesophageal cancer patients and their relationship with resilience. BACKGROUND: Patients with oesophageal cancer face a high number of severe symptoms in the early post-operative period and require the development of an effective symptom management programme. Identifying core symptoms through network analysis helps in accurate patient care. DESIGN: A multicentre cross-sectional study. METHODS: A cross-sectional survey was conducted from August 2022 to August 2023 at three hospitals in Anhui Province, China. A total of 469 patients were recruited for this study and 418 (89.1%) patients completed this investigation. Using network analysis to find early post-operative core symptoms in oesophageal cancer patients. Multiple linear regression was used to analyse resilience factors affecting core symptoms. RESULTS: Sadness was the most core symptom in oesophageal cancer patients in the early post-operative period (rs = 1.41), followed by incision pain and difficulty breathing while resting (rs = 1.20, rs = 1.08). Resilience was significantly associated with patients' feelings of sadness, with optimism having the greatest impact on sadness (p < .01). CONCLUSION: Sadness is the most core symptom in patients in the early post-operative period and special attention should be paid to improving their level of resilience. Local symptoms and dysfunction in the early post-operative period should be treated in a synergistic manner. IMPACT: This study identifies core symptoms and their relationship to resilience in patients with oesophageal cancer in the early post-operative period. Symptoms as the main core symptom in patients in the early post-operative period, which was sadness and was significantly associated with resilience. Precise interventions can be made to target patients' core post-operative symptoms, which can help improve the effectiveness of symptom management. REPORTING METHOD: We have complied with the relevant EQUATOR research reporting checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution in the study.

Small molecule valproic acid enhances ventral patterning of human neural tube organoids by regulating Wnt and Shh signalling.

Valproic acid (VPA), a clinically approved small molecule, has been reported to activate Wnt signalling that is critical for dorsal-ventral (DV) patterning of neural tube. However, little is known about the impact of VPA on DV patterning process. Here, we show that even though VPA has a negative impact on the early formation of human neural tube organoids (hNTOs), it significantly enhances the efficiency of ventrally patterned hNTOs, when VPA is added during the entire differentiation process. RNA sequencing and RT-qPCR analysis demonstrates VPA activates endogenous Wnt signalling in hNTOs. Surprisingly, transcriptome analysis also identifies upregulation of genes for degradation of GLI2 and GLI3 proteins, whose truncated fragment are transcriptional repressors of Shh signalling. The Western-blot analysis confirms the increase of GLI3R proteins after VPA treatment. Thus, VPA might enhance ventral patterning of hNTOs through both activating Wnt, which can antagonise Shh signalling by inducing GLI3 expression, and/or inhibiting Shh signalling by inducing GLI protein degradation. We further obtain results to show that VPA still increases patterning efficiency of hNTOs with a weak influence on their early formation when the initiation time of VPA is delayed and its duration is reduced. Taken together, this study demonstrates that VPA enhances the generation of more reproducible hNTOs with ventral patterning, opening the avenues for the applications of hNTOs in developmental biology and regenerative medicine.

Fe-Catalyzed Fluorosulfonylation of Alkenes via Sulfur Dioxide Insertion: Synthesis of Lactam-Functionalized Alkyl Sulfonyl Fluorides.

A novel Fe-catalyzed fluorosulfonylation of alkenes with Na2S2O4 and N-fluorobenzenesulfonimide (NFSI) for assembling various lactam-functionalized alkyl sulfonyl fluorides is disclosed. In this reaction, Na2S2O4 acts as both an SO2 source and a reductant. Furthermore, the resulting products can be efficiently transformed into valuable chemicals, including sulfonyl esters and sulfonamides, via the sulfur(VI) fluoride exchange (SuFEx) click reaction. Preliminary mechanistic studies suggest that the transformation proceeds through intramolecular radical cyclization, SO2 insertion, sulfite anion formation, and fluorination.